HIV-1Phase 4PIONANCT01192035
PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial
A Phase 4 study testing Efavirenz or Nevirapine and Ritonavir-boosted lopinavir in people with HIV-1, run by University of Aarhus at 1 site in Guinea-Bissau.
Trial summary
BACKGROUND: Since 1996 the combination of three or more drugs has been the mainstay of human immunodeficiency virus (HIV) treatment. The most important types of drugs are called nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1
- What is being tested?
- Efavirenz or Nevirapine and Ritonavir-boosted lopinavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteGuinea-Bissau
- Study dates
- May 2011to Sep 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Antiretroviral treatment (ART) naïve HIV-1 infected patients. Women receiving ART during pregnancy can be included.
- Age ≥ 18 years
- CD4+ cell count ≤ 350 cells/µL and/or
- Clinical signs of immune suppression (WHO clinical stage 3 or 4) irrespective of CD4+ cell count.
Who cannot join
- Tuberculosis (TB) treatment with rifampicin at the time of enrolment.
- Co-infection with HIV-2.
- Grade 3 or 4 alanine transaminase (ALAT) elevation (>5 times upper normal limit).
- Patients with cerebral disturbances that complicates the ability to give informed consent or follow the treatment regime.
Trial locations and contacts
1 site in 1 country.
Guinea-Bissau1 site
Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
Bissau
About this study
Official title: PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
BACKGROUND: Since 1996 the combination of three or more drugs has been the mainstay of human immunodeficiency virus (HIV) treatment. The most important types of drugs are called nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) Response to treatment is measured as increasing CD4+ cell count and decreasing HIV viral load. A major problem is the development of resistance. NNRTIs are recommended as part of first-line treatment of HIV in Africa but many Africans have a slower NNRTI clearance than Caucasians making them more susceptible for development of resistance in case of treatment interruptions. PIs might therefore be a better option in an African setting with low adherence.
AIM: To evaluate two different treatment regimens in HIV-1 infected patients:
Read more
- A NNRTI (efavirenz/nevirapine) based regimen and B) A PI (ritonavir-boosted lopinavir) based regimen with regard to treatment outcomes. HYPOTHESIS: Treatment with a PI will be superior to treatment with a NNRTI due to less development of resistance.
METHODS: Treatment-naïve adult HIV-1 patients enrolled in an existing cohort The West African Retrovirus and Acquired Immune Deficiency (WARAID) cohort in Guinea Bissau with CD4+ cell count ≤ 350 cells/µL and/or clinical signs of immune suppression (World Health Organization (WHO) clinical stage 3 or 4) will be randomised 1:1 to: Treatment A: 2 NRTIs (lamivudine and either zidovudine or stavudine) and 1 NNRTI (efavirenz or nevirapine) or Treatment B: 2 NRTIs (same as in treatment A) and 1 PI (ritonavir-boosted lopinavir). Primary outcome: Viral load suppression <400 copies/ml 12 months after enrolment.
PERSPECTIVES: Guidelines for treatment of HIV in Africa are more or less a copy of the guidelines used in Europe and North America. Genetic differences in pharmacokinetics, more women infected in Africa and difficulties ensuring good adherence mean that results obtained from Caucasian patients are not directly transferrable to African patients. The results of this study will hopefully help guiding the treatment of HIV in Africa in the future. The investigators believe the HIV infected people in West Africa deserve the same evidence-based medicine as in developed countries.
- Conditions
- HIV-1
- Being tested
- Efavirenz or Nevirapine, Ritonavir-boosted lopinavir
- Keywords
- Africa, Western, Antiretroviral Therapy, Highly Active
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavirenz or NevirapineDrug
Also called Stocrin, Sustiva, Viramune
2 NRTIs (lamivudine 150 mg "bis in die - twice a day" (BID) and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 NNRTI (efavirenz 600 mg "omne in die - once daily" (OD) or nevirapine 200 mg OD for the first 2 weeks and after that 200 mg BID). Efavirenz will be used in all male patients according to national HIV guidelines. Pregnant patients and female patients with a child bearing potential will be treated with nevirapine if CD4+ cell count is ≤ 350 cells/mm3 with close monitoring of liver enzymes during the first 12 weeks in patients with CD4+ cell count >250 cells/mm3. Females beyond childbearing age will be treated with efavirenz.
Ritonavir-boosted lopinavirDrug
Also called Kaletra, Aluvia
2 NRTIs (lamivudine 150 mg BID and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 PI (ritonavir-boosted lopinavir 400/100 mg BID).
| Study group | Role | What they receive |
|---|---|---|
| NNRTI | Active comparator | Not described Receives: Drug: Efavirenz or Nevirapine |
| Protease inhibitor | Active comparator | Not described Receives: Drug: Ritonavir-boosted lopinavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fraction of patients with viral load suppression <400 copies/ml
Measured: 12 months after enrolment
Secondary outcomes (9)
Fraction of patients with viral load suppression <50 copies/ml
Measured: 12 months after enrolment
Increment of CD4+ cell count of at least 100 cells/µL
Measured: 12 months after enrolment
Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
Measured: 12 months after enrolment
Frequency of adverse events and severe adverse events
Measured: Within 12 months
Compliance.
Compliance defined as the actual amount of medicine taken compared to the planned amount for the same treatment period. A pill count is carried out at each visit.
Measured: Within 12 months
Incidence of tuberculosis.
Measured: Within 12 months
Death.
Death at 12 month follow-up. Any patient lost to follow-up will be attempted visited at home by a field assistant 1 month after latest visit due. Information on patient death from family or neighbors will be recorded as a mortality event and a verbal autopsy conducted.
Measured: Within 12 months
Weight
Increase in body mass index (BMI) and frequency of severe weight loss (>10% of presumed or measured body weight).
Measured: Within 12 months
Plasma cytokine levels
Measured: Within 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startMay 2011
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital Skejby, Bandim Health Project, Ministry of Public Health, Guinea-Bissau, Abbott
- Responsible party
- Sponsor
- Investigators
- Sanne Jespersen, MD, Principal investigator, Aarhus University Hospital SkejbyAlex L Laursen, MD, DMSc, Study director, Aarhus University Hospital SkejbyLars Oestergaard, Prof MD DMSc, Study director, Aarhus University Hospital SkejbyChristian Wejse, MD, PhD, Study chair, Aarhus University Hospital Skejby
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01192035
- Sponsor's protocol ID
- 11/CNES/2010
- Acronym
- PIONA
- Status last verified
- Nov 2014
- First submitted
- 9 Aug 2010
- Last updated
- 25 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jespersen S, Honge BL, Krarup H, Medstrand P, Sorensen A, Medina C, Te DDS, Correira FG, Erikstrup C, Ostergaard L, Wejse C, Laursen AL; Bissau HIV Cohort study group. Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial. J Acquir Immune Defic Syndr. 2018 Nov 1;79(3):386-393. doi: 10.1097/QAI.0000000000001820.
PubMed 30044302
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
- ClinicalTrials.gov ID
- NCT01192035
- Acronym / sponsor ID
- PIONA / 11/CNES/2010
- Conditions
- HIV-1
- Keywords
- Africa, Western, Antiretroviral Therapy, Highly Active
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital Skejby, Bandim Health Project, Ministry of Public Health, Guinea-Bissau, Abbott
- Study start
- May 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 31 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BACKGROUND: Since 1996 the combination of three or more drugs has been the mainstay of human immunodeficiency virus (HIV) treatment. The most important types of drugs are called nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) Response to treatment is measured as increasing CD4+ cell count and decreasing HIV viral load. A major problem is the development of resistance. NNRTIs are recommended as part of first-line treatment of HIV in Africa but many Africans have a slower NNRTI clearance than Caucasians making them more susceptible for development of resistance in case of treatment interruptions. PIs might therefore be a better option in an African setting with low adherence.
AIM: To evaluate two different treatment regimens in HIV-1 infected patients:
- A NNRTI (efavirenz/nevirapine) based regimen and B) A PI (ritonavir-boosted lopinavir) based regimen with regard to treatment outcomes. HYPOTHESIS: Treatment with a PI will be superior to treatment with a NNRTI due to less development of resistance.
METHODS: Treatment-naïve adult HIV-1 patients enrolled in an existing cohort The West African Retrovirus and Acquired Immune Deficiency (WARAID) cohort in Guinea Bissau with CD4+ cell count ≤ 350 cells/µL and/or clinical signs of immune suppression (World Health Organization (WHO) clinical stage 3 or 4) will be randomised 1:1 to: Treatment A: 2 NRTIs (lamivudine and either zidovudine or stavudine) and 1 NNRTI (efavirenz or nevirapine) or Treatment B: 2 NRTIs (same as in treatment A) and 1 PI (ritonavir-boosted lopinavir). Primary outcome: Viral load suppression <400 copies/ml 12 months after enrolment.
PERSPECTIVES: Guidelines for treatment of HIV in Africa are more or less a copy of the guidelines used in Europe and North America. Genetic differences in pharmacokinetics, more women infected in Africa and difficulties ensuring good adherence mean that results obtained from Caucasian patients are not directly transferrable to African patients. The results of this study will hopefully help guiding the treatment of HIV in Africa in the future. The investigators believe the HIV infected people in West Africa deserve the same evidence-based medicine as in developed countries.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NNRTI | Active comparator | Drug: Efavirenz or Nevirapine |
| Protease inhibitor | Active comparator | Drug: Ritonavir-boosted lopinavir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Antiretroviral treatment (ART) naïve HIV-1 infected patients. Women receiving ART during pregnancy can be included.
- Age ≥ 18 years
- CD4+ cell count ≤ 350 cells/µL and/or
- Clinical signs of immune suppression (WHO clinical stage 3 or 4) irrespective of CD4+ cell count.
Key exclusion criteria (4 listed)
- Tuberculosis (TB) treatment with rifampicin at the time of enrolment.
- Co-infection with HIV-2.
- Grade 3 or 4 alanine transaminase (ALAT) elevation (>5 times upper normal limit).
- Patients with cerebral disturbances that complicates the ability to give informed consent or follow the treatment regime.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efavirenz or NevirapineAlso: Stocrin, Sustiva, Viramune2 NRTIs (lamivudine 150 mg "bis in die - twice a day" (BID) and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 NNRTI (efavirenz 600 mg "omne in die - once daily" (OD) or nevirapine 200 mg OD for the first 2 weeks and after that 200 mg BID). Efavirenz will be used in all male patients according to national HIV guidelines. Pregnant patients and female patients with a child bearing potential will be treated with nevirapine if CD4+ cell count is ≤ 350 cells/mm3 with close monitoring of liver enzymes during the first 12 weeks in patients with CD4+ cell count >250 cells/mm3. Females beyond childbearing age will be treated with efavirenz. | Drug | NNRTI |
| Ritonavir-boosted lopinavirAlso: Kaletra, Aluvia2 NRTIs (lamivudine 150 mg BID and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 PI (ritonavir-boosted lopinavir 400/100 mg BID). | Drug | Protease inhibitor |
Primary outcome
Fraction of patients with viral load suppression <400 copies/ml
Time frame: 12 months after enrolment
9 secondary outcomes
Fraction of patients with viral load suppression <50 copies/ml
Time frame: 12 months after enrolment
Increment of CD4+ cell count of at least 100 cells/µL
Time frame: 12 months after enrolment
Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
Time frame: 12 months after enrolment
Frequency of adverse events and severe adverse events
Time frame: Within 12 months
Compliance.
Time frame: Within 12 months
Incidence of tuberculosis.
Time frame: Within 12 months
Death.
Time frame: Within 12 months
Weight
Time frame: Within 12 months
Plasma cytokine levels
Time frame: Within 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2015.
- Derived from this study: PubMed 30044302Jespersen S, Honge BL, Krarup H, Medstrand P, Sorensen A, Medina C, Te DDS, Correira FG, Erikstrup C, Ostergaard L, Wejse C, Laursen AL; Bissau HIV Cohort study group. Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial. J Acquir Immune Defic Syndr. 2018 Nov 1;79(3):386-393. doi: 10.1097/QAI.0000000000001820.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sanne Jespersen, MD principal investigator
Aarhus University Hospital Skejby
Alex L Laursen, MD, DMSc study director
Aarhus University Hospital Skejby
Lars Oestergaard, Prof MD DMSc study director
Aarhus University Hospital Skejby
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Efavirenz or Nevirapine and Ritonavir-boosted lopinavir in people with HIV-1, run by University of Aarhus at 1 site in Guinea-Bissau.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Guinea-Bissau. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fraction of patients with viral load suppression <400 copies/ml (time frame: 12 months after enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01192035, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2015; AzTrials last refreshed its copy on 7 Nov 2026.